HLA-G is expressed in intestinal samples of ulcerative colitis and Crohn's disease patients and HLA-G5 expression is differentially correlated with TNF and IL-10 cytokine expression

Hum Immunol. 2018 Jun;79(6):477-484. doi: 10.1016/j.humimm.2018.03.006. Epub 2018 Mar 26.

Abstract

HLA-G is an immunomodulatory molecule that can be produced by epithelial cells. Considering that TNF and IL-10 participate in bowel inflammatory disorders and that both cytokines modulate HLA-G, we evaluated HLA-G, TNF and IL-10 mRNA expression by qPCR and HLA-G protein levels by immunohistochemistry in two intestinal samples exhibiting different degree of inflammation within a patient suffering from Crohn's disease (CD) or ulcerative colitis (UC). Tissue HLA-G5 (P < 0.0001), TNF (P = 0.0004) and IL-10 (P = 0.0169) mRNA expression levels were higher in intestinal areas exhibiting intense inflammation compared to areas of low inflammation, and HLA-G protein levels were not associated with degree of mucosal inflammation. In CD, the expression of TNF was correlated with IL-10 in low inflamed areas, exhibiting a TNF:IL-10 ratio = 3, but in inflamed areas the ratio increased to 9-folds. In UC, the expression of TNF was correlated to IL-10, irrespective of the inflammation grade, with little variation of the TNF:IL-10 ratio in the various inflamed areas. TNF and IL-10 expression was correlated with HLA-G5 expression in mild inflamed areas. Both CD and UC samples exhibited gene and protein expression of HLA-G; and the HLA-G5 expression is differentially correlated with TNF and IL-10 levels depending on the type of the underlying inflammatory bowel disorder.

Keywords: Crohn’s disease; HLA-G; IL-10; Inflammatory bowel disease; TNF; Ulcerative colitis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Colitis, Ulcerative / immunology*
  • Crohn Disease / immunology*
  • Disease Progression
  • Epithelial Cells / physiology*
  • Female
  • HLA-G Antigens / metabolism*
  • Humans
  • Immunohistochemistry
  • Immunomodulation
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Intestinal Mucosa / metabolism*
  • Intestines / pathology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • HLA-G Antigens
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10